|
Abuchowski et al., "Immunosuppressive properties and circulating life of achromobacter glutaminase-asparaginase covalently attached to polyethylene glycol in man", Cancer Treat. Rep. 65: 1077-1081, 1981.
|
|
Akiyama, T. et al., "Genistein, a specific inhibitor of tyrosine-specific protein kinases", JBiol Chem 262(12), 5592-5, 1987.
|
|
Allende-Vigo MZ. "Women and metabolic syndrome: an overview of its peculiarities", 2008 P.R. Health Sci. J. 27:190-5.
|
|
Anderson (Chem and Biol 10:787-797, 2003).
*
|
|
Anderson, "The Process of Structure-Based Drug Design" Chem. and Biol. 10, 787-197, 2003.
|
|
Arias-Loza, P. A. et al., "Both estrogen receptor subtypes, alpha and beta, attenuate cardiovascular remodeling in aldosterone salt-treated rats", Hypertension 5(1(2), 432-8, 2007.
|
|
Arias-Loza, P. A., et al, "Both estrogen receptor subtypes, alpha and beta, attenuate cardiovascular remodeling in aldosterone salt-treated rats", Hypertension 5(1(2), 432-8, 2007.
|
|
Ariazi EA et al "Estrogen-Related Receptors as Emerging Targets in Cancer and Metabolic Disorders" 2006 Curr. Top Med. Chem. 6:203-15.
|
|
Ascenzi P., et al., "Structure-function relationship of estrogen receptor alpha and beta: Impact on human health", Mol. Aspects Med. 27 (4) 299-402, 2006.
|
|
Barkhem, T., et al., "Differential response of estrogen receptor alpha and estrogen receptor beta to partial estrogen agonists/antagonists", Mol. Pharmacol. 54(1), 10512, 1998.
|
|
Barros RP et al , "Estrogen receptors: new players in diabetes mellitus" 2006 Trends Mol. Med. 12:425-31.
|
|
Beekum O et al , "Posttranslational Modifications of PPAR-gamma: Fine-tuning the Metabolic Master Regulator" 2009 Obesity (Silver Spring) 17:213-9.
|
|
Billin AN , "PPAR-beta/gamma agonists for Type 2 diabetes and dyslipidemia: an adopted orphan still looking for a home", 2008 Expert Opin. Investig. Drugs 17:1465-71.
|
|
Blizzard, T. A. et al (2004). "Estrogen receptor ligands. Part 7: Dihydrobenzoxathiin SERAMs with bicyclic amine side chains". Bioorg. Med. Chem. Lett. 14(15), 3861-4.
|
|
Blizzard, T. A., "Androstene-3,5-dienes as ER-beta selective SERMs", Bioorg. Med. Chem. Lett. 17(22), 6295-8, 2007b.
|
|
Blizzard, T. A., et al, "Bridged androstenediol analogs as ER-beta selective SERMs", Bioorg Med Chem Lett 17(10), 2944-8, 2007a.
|
|
Bodo, C. and Rissman, E. F. (2006), "New roles for estrogen receptor beta in behavior and neuroendocrinology", Front Neuroendocrinology 27(2), 217-32.
|
|
Booth, E. A., et al. (2007). "The pathway-selective estrogen receptor ligand WAY-169916 reduces infarct size after myocardial ischemia and reperfusion by an estrogen receptor dependent mechanism", J. Cardiovascular Pharmacology, 49(6), 401-7.
|
|
Buchwald et al., "Long-term, continuous intravenous heparin administration by an implantable infusion pump in ambulatory patients with recurrent venous thrombosis.", Surgery 88:507, 1980.
|
|
Byrns et al.; "An Indomethacin Analogues, N-(4-Chlorobenzoyl)-melatonin, s a Selective Inhibitor or Aldo-keto Reductase 1C3 (Type 2 3Alpha-HSD, Type 5 17Beta-HSD, and Prostaglandin F Synthase), a Potential Target for the Treatment of Hormone Dependent and Hormone Independent Malignancies", Biochem Pharmacol. Jan. 15, 2008, vol. 75 No. 2, pp. 484-493.
|
|
Cariou B et al, "FXR: a promising target for the metabolic syndrome?" 2007 Trends Pharmacol. Sci. 28:236-43.
|
|
CAS Registry No. 252061-78-2; 6-hydroxy-1(2H)-isoquinolinone.
|
|
CAS Registry No. 491-30-5; 1(2H)-Isoquinolinone.
|
|
Chadwick, C, et al (2005), "Identification of pathway-selective estrogen receptor ligands that inhibit NF-kappaB transcriptionsal activity", Proc. Natl. Acad. Sci. USA 102(7), 2543-8.
|
|
Chan, K. K., et al (2008), "Estrogen receptor subtypes in ovarian, cancer: a clinical correlation", Obstet. Gynecol. 111(1) 144-51.
|
|
Chan, Y. C. et al.; "Raloxifene Relaxes Rat Pulmonary Arteries and Veins: Roles of Gender, Endothelium, and Antagonism of Ca2+ Influx."; The Journal of Pharmacology and Experimental Therapeutics; 312(3), pp. 1266-1271, 2005.
|
|
Chang, E. C, et al (2006), "Impact of estrogen receptor beta on gene networks regulated by estrogen receptor alpha in breast cancer cells", Endocrinology 147(10), 4831-42.
|
|
Chaum E (2002) "Retinal Neuroprotection by Growth Factors: A Mechanistic Perspecitve" JCB-02s-204.
|
|
Chen, W., et al. (2007), Aza analogues of equol: novel ligands for estrogen receptor beta, Bioorg Med Chem 15(17), 5828-36.
|
|
Chesworth R, et al. (2005), "Estrogen receptor beta selective ligands: discovery and SAR of novel heterocyclic ligands", Bioorg. Med. Chem. Lett. 15(24), 5562-6.
|
|
Chesworth, R., et al. (2004), "Tetrahydroisoquinolines as subtype selective estrogen agonists/antagonists", Bioorg. Med. Chem. Lett. 14(11), 2729-33.
|
|
Christian, R. C, et al (2006). "Initial estrogen receptor (ER)beta, but not ERalpha expression. Is correlated with coronary calcification and atherosclerosis in pre- and postmenopausal women", J.Clin. Endocrinol. Metab. 91(7)j 2713-20.
|
|
Collini M.D. et al. (2004). "7-Substituted 2-phenyl-benzofurans as ER beta selective ligands", Bioorg. Med. Chem. Lett. 14(19), 4925-9.
|
|
Compton, D. R. et al. (2004). "Pyrazolo[1,5-a]pyrimidines: estrogen receptor ligands possessing estrogen receptor beta antagonist activity", J. Med. Chem. 47(24), 5872-93.
|
|
Compton, D. R., et al (2004). "Pyrazolo[1,5-a] pyrimidines as estrogen receptor ligands: defining the orientation of a novel heterocyclic core". Bioorg. Med. Chem. Lett. 14(22), 5681-4.
|
|
Cooke et al, "The obesity pipeline: current strategies in the development of anti-obesity drugs", 2006 Nat. Rev. Drug. Discov. 5:919-31.
|
|
Crabtree JS et al., "Activity of three selective estrogen receptor modulators on hormone-dependant responses in the mouse uterus and mammary gland", Molecular and Cellular Endocrinology, Feb. 12, 2008.
|
|
Cvoro, A., et al. (2008), "Selective estrogen receptor-beta agonists repress transcription of proinflammatory genes", J. Immunol. 180(1), 630-6.
|
|
Cypess AM et al. , "Identification and Importance of Brown Adipose Tissue in Adult Humans" 2009 N. Engl. J. Med. 360:1509-17.
|
|
Day et al.; "Design and validation of specific Inhibotors of 17b-hydroxysteriod dehydrogenases for therapeutic application in breast and prostate cancer, and in endometriosis", Endocrine-Related Cancer (2008), vol. 15, pp. 665,692.
|
|
De Angelis, et al (2005a), "Indazole estrogens: highly selective ligands for the estrogen receptor beta". J. Med. Chem. 4S(4)s 1132-44.
|
|
De Angelis, et al (2005b). "Isocoumarins as estrogen receptor beta selective ligands: Isomers of Isoflavone phytoestrogens and their metabolites", Bioorg. Med. Chem. 13(23), 6529-42.
|
|
Diamanti-Kandarakis et al. (1998) "The Effect of a Pure Anti-androgen Receptor Blocker, Flutamide, on the Lipid Profile in the Polycystic Ovary Syndrome". Journal of Clinical Endocrinology and Metabolism, 1998, 83:2699-2705; esp. abstract; p. col. 1, para 3.
|
|
Dick, G. M. et al. "(Xeno)Estrogen Sensitivity of Smooth Muscle BK Channels Conferred by the Regulatory β1 Subunit, a Study of β1Knockout Mice"; The Journal of Biological Chemistry; 276(48); pp. 44835-44840; (2001).
|
|
Dubey RK, et al., "Phytoestrogens inhibit growth and MAP kinase activity in human aortic smooth muscle cells", Hypertension; 33:177-182, 1999.
|
|
Edsall, R. J., et al. (2003). "ERbeta ligands. Part 1: the discovery of ERbeta selective ligands which embrace the 4-hydroxy-biphenyl template", Bioorg. Med. Chem. 11(16), 3457-74.
|
|
Elloso et al, "Suppression of experimental autoimmune encephalomyelitis using estrogen receptor-selective ligands" Journal of Endocrinology, 2005, vol. 185, 243-252.
|
|
European Search Report for European Application No. 13174659.6 dated Aug. 2, 2013.
|
|
Fabricatore et al, "Obesity", 2006 Annu Rev Clin Psychol 2:357-77.
|
|
Follettie et al "Organ messenger Ribonucleic Acid and plasma proteome Changes in the Adjuvant-Induced Arthritis model: Responses to Diseas Induction and Theraphy with the Estogen Receptor-βSelective Agonist ERB-041" Endocrinology 1472):714-723 (2006).
|
|
Foryst-Ludwig A et al "Metabolic Actions of Estrogen Receptor Beta (ER-beta) are Mediated by a Negative Cross-Talk with PPAR-gamma" 2008 PLoS Genet. 4:e1000108.
|
|
Fotsis, T. et al, (1993). "Genistein, a dietary-derived Inhibitor of in vitro angiogenesis", Proc. Nat.l Acad. Sci. USA 90(7), 2690-4.
|
|
Fotsis, T. et al, (1993). "Genistein, a dietary-derived Inhibitor of in vitro angiogenesis", Proc. Natl. Acad. Sci. USA 90(7), 2690-4.
|
|
Fritzemeier, K. H., et al (2004). Biological effects of ERalpha- and ERbeta-selective estrogens, Ernst Schering Res. Found Workshop (46), 127-50.
|
|
Fritzemeier, K. H., et al (2004)."Biological effects of ERalpha- and ERbeta-selective estrogens". Ernst Schering Res. Found Workshop(46), 127-50.
|
|
Fu X. H., et al (2008). "Synthesis of genistein derivatives and determination of their protective effects against vascular endothelial cell damages caused by hydrogen peroxide" Bioorg. Med. Chem. Lett. 18(2), 513-7.
|
|
Fu X. H., et al (2008). "Synthesis of genistein derivatives and determination of their protective effects against vascular endothelial cell damages caused by hydrogen peroxide", Bioorg. Med. Chem. Lett. 18(2), 513-7.
|
|
Geer et al "Gender Differences in Insulin Resistance, Body Composition, and Energy Balance" 2009 Gend. Med. 6 Suppl. 1:60-75.
|
|
Goodson, "Dental Applications", Medical Applications of Controlled Release, supra, vol. 2, pp. 116-138, 1984.
|
|
Green, Kl A., and Carroll, J. S (2007). "Oestrogen-receptor-mediated transcription and the influence of co-factors and chromatin state", Nat. Rev. Cancer 7(9), 713-22.
|
|
Green, KL A., and Carroll, J. S (2007). "Oestrogen-receptor-mediated transcription and the influence of co-factors and chromatin state". Nat. Rev. Cancer 7(9), 713-22.
|
|
Greene, G. L., Shiau A. K., and Nettles, K. W. (2004). "A structural explanation for ERalpha/ERbeta SERM discrimination". Ernst Schering Res Found Workshop (46), 33-45.
|
|
Greene, G. L., Shiau A. K., and Nettles, K. W. (2004). A structural explanation for ERalpha/ERbeta SERM discrimination. Ernst Schering Res Found Workshop (46), 33-45.
|
|
Gungor T. et al., "Synthesis and characterization of 3-arylquinazolinone and 3-arylquinazolinethione derivatives as selective estrogen receptor beta modulators" J. Med. Chem., 49, 2440-2455, 2006.
|
|
Güngör, T. et al. (2006) "Synthesis and Characterization of 3-Arylquinazolinone and 3- Arylquinazolinethione Derivatives as Selective Estrogen Receptor Beta Modulators", J. Med. Chem. 2006, 49, 2440-2455.
|
|
Güngör, T. et al. (2006) "Synthesis and Characterization of 3-Arylquinazolinone and 3-Arylquinazolinethione Derivatives as Selective Estrogen Receptor Beta Modulators". J. Med. Chem. 2006, 49, 2440-2455.
|
|
Gupta, A. K., et al (2007). "QSAR analysis of indazole estrogens as selective beta- estrogen receptor ligands: rationalization of physicochemical properties", Med Chem 3(4), 347-53.
|
|
Gupta, A. K., et al (2007). "QSAR analysis of indazole estrogens as selective beta- estrogen receptor ligands: rationalization of physicochemical properties", Med. Chem. 3(4), 347-53.
|
|
Gustafsson, J. A. (2006). "ERbeta scientific visions translate to clinical uses", Climacteric 9(3) 156-60.
|
|
Haas, E. et al.; "Differential Effects of 17β-Estradiol on Function and Expression of Estrogen Receptor α, Estrogen Receptor β, and GPR30 in Arteries and Veins of Patients with Atherosclerosis"; Hypertension 49(6); pp. 1358-1363; (2007).
|
|
Han, "Advances in characterization of pharmaceutical hydrates", Trends in Bio/Pharmaceutical Industry, pp. 25-29, 2006.
|
|
Harrington, W, et al. (2003), "Activities of estrogen receptor alpha- and beta-selective ligands at diverse estrogen responsive gene sites mediating transactivation or transrepression". Mol. Cell Endocrinol. 206(1-2), 13-22.
|
|
Harris et al "Characterization of the Biological Roles of the Estrogen Receptors, ERα-Selective Ligand" Endocrinology 143 (11):4172-4177 (2002).
|
|
Harris HA "Estrogen Receptor--: Recent Lessons from in Vivo Studies" 2007 Mol. Endocrinol. 21:1-13.
|
|
Harris HA "Estrogen Receptor-—: Recent Lessons from in Vivo Studies" 2007 Mol. Endocrinol. 21:1-13.
|
|
Harris HA., "The unexpected science of estrogen receptor-β selective agonists: a new class of anti-inflammatory agents?" Nuclear Receptor Signaling, 2006, pp. 1-4.
|
|
Harris, H. A. (2006). "The unexpected science of estrogen receptor-beta selective agonists; a new class of anti-inflammatory agents?" Nucl. Recept. Signal 4, eO12.
|
|
Harris, H. A. (2007). "Estrogen receptor-beta: recent lessons from, in vivo studies", Mol. Endocrinol. 21(1), 1-13.
|
|
Harris, H. A., et al (2003), "Evaluation of an estrogen receptor-beta agonist in animal models of human disease". Endocrinology 144(10), 4241-9.
|
|
Hayashi, A., et al (1997). "Genistein, a protein tyrosine kinase inhibitor, ameliorates retinal degeneration after ischemia-reperfusion injury in rat". Invest. Opthalmol. Vis. Sci. 38(6), 1193-202.
|
|
Hellwinkel et al, "Synthesis of heterocycles with MF/A1203 base-systems: 2-arylbenzofurans and 2,3-diarylisoquinolin-1(2H)-ones", Synthesis 9: 1135-1141, 1995, STN Search Report Accession No. 1995:866647.
|
|
Henke, B. R., et al (2002). ,,A new series of estrogen receptor modulators that display selectivity for estrogen receptor beta J. Med. Chem. 45(25), 5492-505.
|
|
Heynekamp, J. J., et al (2006). "Substituted trans-stilbenes, including analogues of the natural product resveratrol, inhibit the human tumor necrosis factor alpha-induced activation of transcription factor nuclear factor kappaB". J. Med. Chem. 49(24), 7182-9.
|
|
Hillisch, A., et al. (2004b). "Dissecting physiological roles of estrogen receptor alpha and beta with potent selective ligands from structure-based design", Mol. Endocrinol. 18(7), 1599-609.
|
|
Ho, S. M. (2004). "Estrogens and anti-estrogens: key mediators of prostate carcinogenesis and new therapeutic candidates". J. Cell Biochem. 91(3), 491-503.
|
|
Hoekstra, W.J., et al. (2005) :Discovery of novel quinoline-based estrogen receptor ligands using peptide interaction profiling, J. Med. Chem. 48(6), 2243-7.
|
|
Imamov, O., et al (2005). "Estrogen receptor beta in health and disease". Biol. Reprod. 73(5) 866-71.
|
|
Imamov, O., et al. (2004). "Estrogen receptor beta in prostate cancer". N. Engl. J. Med. 351(26), 2773-4.
|
|
Inoue et. al., "Acute and chronic effects of T-1032, a novel selective phosphodiesterase type 5 inhibitor, on monocrotaline-induced pulmonary hypertenstion in rats", Biol. Pharm. Bull., , 1422-1426, (2002).
|
|
International Search Report for PCT Application No. PCT/US13/58506 dated Jan. 22, 2014.
|
|
Jazbutyte, V. et al. (2008). "Ligand-dependent activation of ER{beta} lowers blood pressure and attenuates cardiac hypertrophy in ovariectomized spontaneously hypertensive rats". Cardiovasc. Res. 77(4), 774-81.
|
|
Kai M., et al (2004). "Soybean isoflavones eliminate nifedipine-induced flushing of tail skin in ovariectomized mice". J. Pharmacol. Set. 95(4), 476-8.
|
|
Kaja, "Estrogen protects the inner retina from apoptosis and ischemia-induced loss of Vsl-1L/Homer 1C immunoreactive synoptic connections" Inv. Opthalmol and Vis. Sci, Jul. 2005, vol. 44, No. 7, pp. 3155-3162.
|
|
Kajta, M. et al., "Genistein inhibits glutamate-induced apoptosis in primary neuronal cell cultures of mouse brain cortex and cerebellum". Behav Pharmacol: 549 (EBPS Workshop, Abstract P27), 2006.
|
|
Kajta, M., et al. (2007). "Genistein inhibits glutamate-induced apoptotic processes in primary neuronal cell cultures: an involvement of aryl hydrocarbon receptor and estrogen receptor/glycogen synthase kinase-3beta intracellular signaling pathway", Neuroscience 145(2), 592-604.
|
|
Kalin MF, et al, "Sex hormones and coronary disease: a review of the clinical studies", Steroids; 55:330-352, 1990.
|
|
Karas RH, et al., "Human Vascular smooth muscle cells contain functional estrogen receptor", Circulation, 89:1943-1950, 1994.
|
|
Karas, R. H., et al. (1998), "Growth factor activation of the estrogen receptor in vascular cells occurs via a mitogen-activated protein kinase-independent pathway". J. Clin. Invest. 101(12), 2851-61.
|
|
Katre et al., "Chemical modification of recombinant interleukin 2 by polyethylene glycol increases its potency in the murine Meth A sarcoma model" Proc. Natl. Acad. Sci., vol. 84, pp. 1487-1491, 1987.
|
|
Katzenellenbogen J. A. et al, "Workshop 1.4: Nature of the ligand-binding pocket of estrogen receptor alpha and beta: The search for subtype-selective ligands and implications for the prediction of estrogenic activity", Pure Appl. Chem, 75(11-12), 2397-2403, 2003.
|
|
Kersten S "Peroxisome proliferator activated receptors and lipoprotein metabolism", 2008 PPAR Res 2008:132960 (From Example 23.14).
|
|
Kim, S et al (2004), "Estrogen receptor ligands. Part 4: The SAR of the syn-dihydrobenzoxathiin SERAMs". Bioorg. Med. Chem. Lett. 14(11), 2741-5.
|
|
Kintscher U et al, "INT-131, a PPAR-gamma agonist for the treatment of type 2 diabetes", 2009 Curr. Opin. Investig. Drugs 10:381-7.
|
|
Koehler K., et al., (2005). "Reflections on the discovery and significance of estroger receptor beta", Endocr. Rev. 26(3), 465-78.
|
|
Krishnan, G. et al., "Pharmacological actions of a selective estrogen receptor beta (ER beta} agonist in ovarlectomized rats", J. Bone Miner. Res. 20(Suppl. 1): Abst SA427. 27th Annual Meeting American Society Bone Miner. Res. (ASBHR) (Sep. 23-27r Nashville, United States), 2005.
|
|
Kuiper, G.G. et al. (1997). "Comparison of the ligand binding specificity and transcript tissue distribution of estrogen receptors alpha and beta". Endocrinology 138(3), 863-70.
|
|
Lai K et al "Estrogen Receptor -Regulates Expression of the Orphan Receptor Small Heterodimer Partner" 2003 J. Biol. Chem. 278:36418-29 (From Example 23.14).
|
|
Lai K et al "Estrogen Receptor —Regulates Expression of the Orphan Receptor Small Heterodimer Partner" 2003 J. Biol. Chem. 278:36418-29 (From Example 23.14).
|
|
Lai S., et al (2004). "Metastases of prostate cancer express estrogen receptor-beta". Urology 64(4), S14-20.
|
|
Langer, "New methods of Drug Delivery", Science 249:1627-1633, 1990.
|
|
Lavie et al, "Obesity and Cardiovascular Disease: Risk Factor, Paradox, and Impact of Weight Loss" 2009 J. Am. Coll. Cardiol. 53:1925-32.
|
|
Leung, Y.K., et al (2006). ,,Estrogen receptor (ER)-beta isoforms: a key to understanding ER-Beta signaling. Proc. Natl. Acad. Sci. USA 103(35), 13162-7.
|
|
Leventhal et al., "An estrogen receptor-β agonist is active in models of inflammatory and chemical-induced pain" European Journal of Pharmacology, 553: 146-148, 2006.
|
|
Liang YQ et al "Estrogen receptor beta is involved in the anorectic action of estrogen", 2002 Int. J. Obes. Relat. Metab. Disord. 26:1103-9.
|
|
Lindner V, et al, "Increased expression of ER b mRNA in male blood vessels following vascular injury", Circ. Res., 83:224-229, 1998.
|
|
Lopez-Berestein, "Treatment of systemic fungal infections with liposomal-amphotericin B" Liposomes in the Therapy of Infectious Disease and Cancer, Lopez- Berestein and Fidler (eds.), pp. 317-327, 1989.
|
|
Luan F., et al., (2008) "Classification of estrogen receptor-beta ligands on the basis of their binding affinities using support vector machine and linear discriminant analysis". Eur. J. Med. Chem. 43(1), 43-52.
|
|
Lund, T. D., et al (2004a), "Androgen receptor expression in the rat prostate is down-regulated by dietary phytoestrogens". Reprod. Biol. Endocrinol. 2, 5.
|
|
Lund, T.D et al (2004b). "Equal is a novel anti-androgen that inhibits prostate growth and hormone feedback". Biol. Reprod. 70(4), 1188-95.
|
|
Lutty, G. et al (1999). "Changes in choriocapiliaris and retinal pigment epithelium in age-related macular degeneration". Mol. Vis. 5, 35.
|
|
Mahajan et. al.; "T-1032, a cyclic GMP phosphodiesterase-5 inhibitor, acutely blocks physiologic insulin-mediated muscle haemodynamic effects and glucose uptake in vivo", British J Pharmaco, vol. 140(7), 1283-1291, (2003).
|
|
Malamas, M.S., et al. (2004). "Design and synthesis of aryl diphenolic azoles as potent and selective estrogen receptor-beta ligands". J. Med. Chem. 47(21), 5021-40.
|
|
Manas, E.S.,et al (2004), "Structure-based design of estrogen receptor-beta selective ligands". J.Arn. Chem. Soc. 126(46), 1510649.
|
|
McDevitt, R. E., et al. (2005). "Estrogen receptor ligands: design and synthesis of new 2-arylindene-1-ones". Bioorg. Med. Chem. Lett. 15(12), 3137-42.
|
|
Mckinnon et al. (2003) "Glaucoma: ocular Alzheimer's disease? Frontiers in Bioscience" 8:s 1140-1156, esp, abstract; p. 1141, col. 2, para 2; p. 1150, col. 1, para 2.
|
|
McPherson, S. J., et al. (2006). "The role of ERalpha and ERheta in the prostate: insights from genetic models and isoform-selective ligands". Ernst Schering Found Symp. Proc. 1, 131-47.
|
|
Mendelsohn ME et al. "Mechanism of disease: the protective effects of estrogen on the cardiovascular system", N. England J. Med., 340:1801-1811, 1999.
|
|
Mewshaw, R, E. et al. (2007). "ERbeta ligands. Part 5: synthesis and structure-activity relationships of a series of 4′-hydroxyphenyl-aryl-carbaldehyde oxime derivatives". Bioorg. Med. Chem. Lett. 17(4), 902-6.
|
|
Mewshaw, R. E., et al (2005). "ERbeta ligands. 3. Exploiting two binding orientations of the 2-phenylnaphthalene scaffold to achieve ERbeta selectivity". J. Med. Chem. 48(12), 3953-79.
|
|
Meyers et al. (2001) "Estrogen Receptor βPotency-Selective Ligands: Structure-Activity Relationship Studies fo Diarylpropionitriles and Their Acetylene and Polar Analogues" J..Med. Chem. 44, 4230-4251.
|
|
Miller, C. P., et al. (2003). "Constrained phytoestrogens and analogues as ERbeta selective ligands", Bioorg. Med. Chem. Lett. 13(14), 2399-403.
|
|
Minutolo, F., et al. (2008). "Monoaryl-substituted salicylaldoximines as ligands for estrogen receptor Beta". J. Med. Chem. 51(5), 1344-51.
|
|
Morani A et al "Biological functions and clinical implications of oestrogen receptors alfa and beta in epithelial tissues", 2008 J. Intern. Med. 264:128-42 (From Example 22A).
|
|
Morani, A. et al (2006). "Lung dysfunction causes systemic hypoxia in estrogen receptor beta knockout (ERbeta−/−) mice". Proc. Natl. Acad. Set. USA 103(18), 7165-9.
|
|
Morissette, M et al., (2008), "Contribution of estrogen receptors alpha and beta to the effects of estradiol in the brain". J. Steroid Biochem. Mol. Biol. 108(3-5), 327-38.
|
|
Munaut "Presence of Estreogen receptor type beta in human retina" Br. J. Opthalmol. 2001; 85: 877-882.
|
|
Muthyala, R, et al (2003). "Exploration of the bicyclo[3.3.1]nonane system as a template for the development of new ligands for the estrogen receptor". Bioorg. Med. Chem. Lett. 13(24). 4485-8.
|
|
Muthyala, R. et al. (2003), "Bridged bicyclic-cores containing a 1,1-diarylethylene motif are high-affinity subtype-selective ligands for the estrogen receptor", J. Med. Chem. 46(9), 1589-602.
|
|
Nakajima "Normalization of retinal vascular permeability in experimental diabetes with genistein" Inv. Opthalmol and Vis. Sci, Aug. 2001, vol. 42, No. 9, pp. 2110-2114.
|
|
Nakajima, M, et al. (2001). "Normalization of retinal, vascular permeability in experimental diabetes with genistein". Invest. Ophthalmol. Vis. Sci. 42(9),2U0-4.
|
|
Narayanan et al.; "Cyclin-dependent kinase activity is required for progesterone receptor function: novel role for cyclin A/Cdk2 as a progesterone receptor coactivator", Mol Cell Biol 25(1):264-277, 2005.
|
|
Narayanan et al.; "Human progesterone receptor displays cell cycle-dependent changes in transcriptional activity", Mol Cell Biol 25(8):2885-2898, 2005.
|
|
Nishigori H et al "Mutations in the Small Heterodimer Partner Gene are Associated with Mild Obesity in Japanese subjects" 2001 Proc. Natl. Acad. Sci. U S A 98:575-80 (From Example 23.14).
|
|
Norman, B. H., et al. (2006). "Benzopyrans are selective estrogen receptor beta agonists with novel activity in models of benign prostatic hyperplasia", J. Med. Chem. 49(21) 6155-7.
|
|
Norman, B. H., et al. (2007). "Benzopyrans as selective estrogen receptor beta agonists (SERBAs). Part 4: functionalization of the benzopyran A-ring". Bioorg. Med. Chem. Left 17(18), 5082-5.
|
|
Office Action issued on Apr. 13, 2015 for Russian Patent Application No. 2012151846.
|
|
Office Action issued on Nov. 11, 2014 for Japanese Application No. 2013-271202.
|
|
Ogueta "Estrogen receptor in the human eye: influence of gender and age on gene expression" Inv. Opthalmol and Vis. Sci, Aug. 1999, vol. 40, No. 9, pp. 1906-1911.
|
|
Ohshiro, K. et al. (2006). "Biological role of estrogen receptor beta in salivary gland adenocarcinoma cells". Clin. Cancer Res. 12(20 Pt I\ 5994-9.
|
|
Palanki M. et al. (2007) "Development of Prodrug 4-Chloro-3-(5-methyl-3{[4-(2-pyrrolidin-1-ylethoxy) phenyl]amino}-1,2,4-benzotriazin-7-yl)phenyl Benzoate (TG100801): A Topically Administered Therapeutic Candidate in Clinical Trials for the Treatment of Age-Related Macular Degeneration" J..Med..Chem.
|
|
Pallottini V et al "Estrogen Regulation of Adipose Tissue Functions: Involvement of Estrogen Receptor Isoforms" 2008 Infect. Disord. Drug Targets 8:52-60.
|
|
Parker, D.L., et al. (2006), "Triazoio-tetrahydrofluorenones as selective estrogen receptor beta agonists". Bioorg. Med. Chem. Lett. 16(17), 4652-6.
|
|
Penning et al.; "Structure-function of human 3 alpha-hydroxysteroid dehydrogenases: genes and proteins", Mol Cell Endocrinol, 215: 63-72, 2004.
|
|
Pike, A, et al. (1999). "Structure of the ligand-binding domain of oestrogen receptor beta in, the presence of a partial agonist and a MI antagonist" Embo. J. 18(17) 4608-18.
|
|
Pinthus et al. (2007) "Androgen Induces Adaptation to Oxidative Stress in Prostate Cancer: Implications for Treatment with Radiation Theraphy", Neoplasia, vol. 9:68-80, esp. Abstract; p. 70, col. 2, para 6; p. 71, col. 1, para 2.
|
|
Pinto de Souza (Indian J Chem, 29B:961-965, 1990).
*
|
|
Pinto de Souza et al., "Synthesis of 3-methyl-1-(2H)-isoquinolinone derivates and their biological activities", Ind. J. Chem. B. Org. 29B(10): 961-965, 1990.
|
|
Pravettoni, A., et al. (2007). "Estrogen receptor beta (ERbeta) and inhibition of prostate cancer cell proliferation: studies on the possible mechanism of action in DU145 cells". Mol. Cell Endocrinol. 263(1-2), 46-54.
|
|
Price et al. (2006) "Toremifene for the Prevention of Prostate Cancer in Men with High grade prostatic Intraephlthelial neoplasia; Results of a Double-Blind, Placebo Controlled, Phase iiB Clinical Trial" The Journal of Urology, 176:965-971, abstract only.
|
|
Prossnitz, E R., et al. (2008). "GPR30; a novel therapeutic target in estrogen-related disease", Trends Pharmacol. Sci. 29(3% 116-23.
|
|
Qin C, et al., (2008) "Understanding the Cardioprotective Effects of Flavonols: Discovery of Relaxant Flavonols without Antioxidant Activity". J. Med. Chem. 51(6) 1874-84.
|
|
Qiu et al.; "Crystal structures of the multispecific 17beta-hydroxysteroid dehydrogenase type 5: critical androgen regulation in human peripheral tissues", Mol Endocrinol, 18: 1798-1807, 2004.
|
|
Reisin et al , "Obesity and Hyper tension: Mechanisms, Cardio-Renal Consequences, and Therapeutic Approaches", 2009 Med. Clin. North Am. 93:733-51.
|
|
Remmers et al. (1997) "Testosterone receptor blockade after trauma-hemorrhage improves cardiac and hepatic functions in males" Am. J. Physiol.-Heart Circ. Physiol., 287: 2919-2925, esp abstract, p. H2924, col. 1.
|
|
Remmers et al. (1997) "Testosterone receptor blockade after trauma-hemorrhage improves cardiac and hepatic functions in males" Am. J. Physiol.—Heart Circ. Physiol., 287: 2919-2925, esp abstract, p. H2924, col. 1.
|
|
Rhodes, M. E. et al. (2006), "ERbeta-selective SERMs produce mnemonic-enhancing effects in the inhibitory avoidance and water maze tasks". Neurobiol. Learn Mem. 85(2), 183-91.
|
|
Richardson, T.L., et al. (2007b). "Benzopyrans as selective estrogen receptor beta agonists (SERBAs). Part 5: Combined A- and C-ring structure-activity relationship studies". Bioorg. Med. Chem. Lett. 17(20), 5563-6.
|
|
Richardson, TL., et al. (2007c). "Benzopyrans as selective estrogen receptor beta agonists (SERBAs). Part 2: structure-activity relationship studies on the benzopyran scaffold". Bioorg. Med. Chem. Lett. 17(13), 3570-4.
|
|
Richardson. T. L., et al. (2007a), "Benzopyrans as selective estrogen receptor beta agonists (SERBAs). Part 3: synthesis of cyclopentanone and cyclohexanone intermediates for C-ring; modification". Bioorg. Med. Chem. Lett. 17(17), 4824-8.
|
|
Roelens, F., et al. (2006). "Subtle side-chain modifications of the hop phytoestrogen 8-prenylnaringenin result in distinct agonist/antagonist activity profiles for estrogen receptors alpha and beta". J. Med. Chem. 49(25)48 7357-65.
|
|
Roman et al.; "Association of Carotid Atherosclerosis and Left Ventricular Hypertrophy", JACC, vol. 25 No. 1, pp. 83-90, Jan. 1995.
|
|
Rose et al.; "The effects of a low-fat dietary intervention and tamoxifen adjuvant therapy on the serum estrogen and sex hormone-binding globulin concentrations of postmenopausal breast cancer patients", Breast Cancer Research and Treatment, 1993, vol. 27:253-262, p. 253.
|
|
Safe, S., et al. (2006). "The role of xenoestrogenic compounds in the development of breast cancer". Trends Pharmacol. Sci. 27(8), 447-54.
|
|
Saudek et al., "A preliminary trial of the programmable implantable medication system for insulin delivery.", N. Engl. J. Med. 321:574, 1989.
|
|
Schopfer U. et al (2002) "Toward Selective Erβ Agonists for Central Nervous System Disorders: Synthesis and Characterization of Aryl Benzthiophenes" J..Med..Chem. 45, 1399-1401.
|
|
Sefton, "Implantable pumps", CRC Crit. Ref. Biomed. Eng. 14:201 (1987).
|
|
Seo J. et al. (2006). "Fluorine-substituted cyclofenil derivatives as estrogen receptor ligands: synthesis and structure-affinity relationship study of potential positron emission tomography agents for imaging estrogen receptors in breast cancer". J. Med. Chem. 49(8)7 2496-511.
|
|
Setchell K. D. (2006), "Assessing risks and benefits of genistein and soy". Environ. Health Perspect. 114(6), A332-3.
|
|
Setchell, K. D., et al. (2005). "S-equol, a potent ligand for estrogen receptor beta, is the exclusive enantiomeric form of the soy isoflavone metabolite produced by human intestinal bacterial flora", Am. J. Gin. Nutr. 81(5), 1072-9.
|
|
Shen, S. S, et al. (2006). "Expression of estrogen receptors-alpha and -beta in bladder cancer cell lines and human bladder tumor tissue". Cancer 106(12), 2610-6.
|
|
Shiau, A. K, et al. (2002). "Structural characterization of a subtype-selective ligand reveals a novel mode of estrogen receptor antagonism". Nat. Struct. Biol. 9(5), 359-64.
|
|
Siow RCM, et al, Cardiovascular targets for estrogens and phytoestrogens; Transcriptional regulation of nitric oxide synthase and antioxidant defense genes. Free Radical biology and Medicine; 42:909-925, 2007.
|
|
Skliris G.P. et al., (2008) "Estrogen receptor alpha negative breast cancer patients: Estrogen receptor beta as a therapeutic target" J. Steroid Biochem. Mol. Biol. 109(1-2), 140.
|
|
Soderberg et al.; "Direct observation of individual endogenous protein complexes in situ by proximity ligation", Nat Methods, 3: 995-1000, 2006.
|
|
Somjen, D., et al (2002), "6-Carboxymethyl genistein: a novel selective oestrogen receptor modulator (SERM) with unique, differential, effects on the vasculature, bone -and uterus". J. Endocrinol. 173(3), 415-27.
|
|
Stanbrough et al.; "Increased expression of genes converting adrenal androgens to testosterone in androgen-independent prostate cancer", Cancer Res, 66: 2815-2825, 2006.
|
|
STN Search Report and Summary (Accession No. 2004:41298).
*
|
|
Strom, A., et al. (2004). "Estrogen receptor beta inhibits 17beta-estradiol-stimulated proliferation of the breast cancer cell line T47D". Proc. Natl. Acad. Sci. USA 101(6) 1566-71.
|
|
Sun, J., et al (2003). "Molecular basis for the subtype discrimination of the estrogen receptor-beta-selective ligand, diarylpropionitrile". Mol. Endocrinol. 17(2), 247-58.
|
|
Sun, W. et al., "6H-Benzo[c]chromen-6-one derivatives as selective ERbeta agonists" 230th ACS Natl Meet (Aug. 28-Sep. 1, Washington DC), Abst MEDI 25, 2005.
|
|
Sun, Wet al. (2006). "6H-Benzo[c]chromen-6-one derivatives as selective ERbeta agonists". Bioorg. Med. Chem. Lett. 16(6), 1468-72.
|
|
Supplementary European Search Report for European Application No. 11778267.2 dated Oct. 7, 2013.
|
|
Szkudelska, K., and Nogowski, L. (2007). "Genistein-a dietary compound inducing hormonal and metabolic changes". J. Steroid. Biochem. Mol. Biol. 105(1-5), 37-45.
|
|
Takahashi, W., et al. (1997). "Effect of estrogen on nitric oxide-induced relaxation of the rabbit urethra". Eur. J. Pharmacol. 339(2-3), 165-71.
|
|
Tan, Q et al. (2004a). "Estrogen receptor ligands. Part 5: Tue SAR of dihydrobenzoxathiins containing modified basic side chains". Bioorg. Med. Chem. Lett. 14(14), 3747-51.
|
|
Tan, Q. et al. (2004b). "Estrogen receptor ligands. Part 6: Synthesis and binding affinity of dihydrobenzodithiins". Bioorg. Med. Chem. Lett. 14(14), 3753-5.
|
|
Thiel (Nature Biotechnol 2:513-519, 2004).
*
|
|
Thiel, "Structure-aided drug design's next generation" Nature Biotechnol. 2, 513-519, 2004.
|
|
Thomas et al, "Targeting bile-acid signaling for metabolic diseases", 2008 Nat. Rev. Drug Discov. 7:678-93.
|
|
Tiwari-Woodruff, S., e tal (2007). "Differential neuroprotective and antiinfiammatory effects of estrogen receptor (ERalpha and ERbeta ligand treatment". Proc. Natl. Acad. Sci. USA 104(37), 14813-8.
|
|
Tontonoz P et al "Fat and Beyond: The Diverse Biology of PPAR-gamma" 2008 Annu. Rev. Biochem. 77:289-312 (From Example 23.14).
|
|
Traupe, T. et al. (2007). "Distinct roles of estrogen receptors alpha and beta mediating acute vasodilation of epicardial coronary arteries". Hypertension 49(6)1364-70.
|
|
Treat et al, "Liposomes in the Therapy of Infectious Disease and Cancer" Liss, New York pp. 353-365, 1989.
|
|
Treeck, O., et al. (2007). "Novel estrogen receptor beta transcript variants identified in human breast cancer cells affect cell growth and apoptosis of COS-1 cells". Mol. Cell Endocrinol. 264(1-2) 50-60.
|
|
Tremblay, A., et al. (1999). "Ligand-independent recruitment of SRC-1 to estrogen receptor beta through phosphorylation of activation function AF-1". Mol. Cell 3(4), 513-9.
|
|
Trotter, B. W., et al. (2006). "Design and synthesis of novel isoquinoline-3-nitriles as orally bioavailable Kv1.5 antagonists for the treatment of atrial fibrillation". J. Med. Chem. 49(24), 6954-7.
|
|
Turgeon JL et al "Complex Actions of Sex Steroids in Adipose Tissue, the Cardiovascular System, and Brain: Insights from Basic Science and Clinical Studies" 2006 Endocr. Rev. 27:575-605 (From Example 23.13).
|
|
U.S. Appl. No. 09/519,079, filed Mar. 6, 2000, Robl et al.
|
|
Ullrich, J. W. et al. (2007). "Estrogen receptor beta ligands: design and synthesis of new 2-phenyl-isoindole-1,3-diones", Bioorg. Med. Chem. Lett. 17(1), 118-22.
|
|
Ullrich, J.W. et al., "4-Hydroxy-N-phenyl substituted phthalimides as selective estrogen receptor beta (ER.b) ligands", 230th ACS Nat! Meet (Aug. 28-Sep. 1, Washington DC), Abst MEDI 27 (Wyeth), 2005.
|
|
Veeneman, "Non-steroidal subtype selective endrogens", Current Medicinal Chemistry, vol. 12, No. 9, 2005, pp. 1077-1136.
|
|
Vippagunta et al., "Crystalline solids" Adv. Drug Rev. 48: 3-26, 2001.
|
|
Vivacqua, A. et al. (2006); "The G protein-coupled receptor GPR30 mediates the proliferative effects induced by 17beta-estradiol and hydroxytamoxifen in endometrial cancer cells", Mol. Endocrinol. 20(3), 631-46.
|
|
Vu, A. T, et al. (2007). "ERbeta ligands. Part 6; 6H-Chromeno[4,3-b]quinolines as a new series of estrogen receptor beta-selective ligands". Bioorg. Med. Chem. Lett. 17(14), 4053-6.
|
|
Vu, A. T., et al. (2005). "ERbeta ligands. Part 4: Synthesis and structure-activity relationships of a series of 2-phenyiquinoline derivatives". Bioorg. Med. Chem. Lett. 15(20), 4520-5.
|
|
Wada-Hirake O, et al, "Role of estrogen receptor beta in uterine stroma and epithelium: insights from estrogen receptor beta −/− mice", PNAS, 103(48):18350-5, 2006.
|
|
Walker, H. A, et al. (2001). "The phytoestrogen genistein produces acute nitric oxide-dependent dilation of human forearm vasculature with similar potency to 17beta-estradiol." Circulation 103(2), 258-62.
|
|
Wang, Y., et al. (2006), "A second binding site for hydroxytamoxifen within the coactivator-binding groove of estrogen receptor beta". Proc. Natl. Acctd. Sci. USA 103(26), 9908-fl.
|
|
Wang. S. F.. et al, (2005). "Genistein derivatives as selective estrogen receptor modulators: sonochemical synthesis and in vivo anti-osteoporotic action". Bioorg. Med. Chem. 13(16) 4§80-90.
|
|
Waring, R. H., et al. (2008). "Phytoestrogens and xenoestrogens: the cotribution of diet and environment to endocrine disruption". J. Steroid. Biochem. Mol. BM 108(3-5), 213-20.
|
|
Weihua, Z., et al. (2002). "An endocrine pathway in the prostate, ERbeta, AR, 5alpha-androstane-3beta,17beta-diol, and CYP7B1, regulates prostate growth". Proc. Natl. Acad. Sci. USA 99(21), 13589-94.
|
|
Wenger NK, et al, "Cardiovascular health and disease in women", N. England J. Med., 329:247-256, 1993.
|
|
Wildonger, K. L., et al (2006). "Tetrahydrofluorenones with conformationally restricted side chains as selective estrogen receptor beta ligands". Bioorg. Med. Chem. Lett. 16(17), 4462-6.
|
|
Wilkening, R. R. (2006) "The discovery of tetrahydrofluorenones as a new class of estrogen receptor beta-subtype selective ligands". Bioorg. Med. Chem. Lett. 16(13) 3489-94.
|
|
Wilkening, R. R., et al. (2006a). "Estrogen receptor beta-subtype selective tetrahydrofluorenones: use of a fused pyrazole as a phenol bioisostere", Bioorg. Med. Chem. Lett. 16(15), 3896-901.
|
|
Wu et al.; "Meta-Analysis: Dietary Fat Intake, Serum Estrogen Levels, and the irsk of Breast Cancer", Journal of the National Cancer Institute, Mar. 17, 1999, vol. 91, No. 6.
|
|
Yager, "Mitochondrial estrogen receptors-new insights into specific functions", Trends in Endocr. and Metabol., vol. 18, No. 3, pp. 89-91, 2007.
|
|
Yager, "Mitochondrial estrogen receptors—new insights into specific functions", Trends in Endocr. and Metabol., vol. 18, No. 3, pp. 89-91, 2007.
|
|
Yang, C. et al. (2004a). "ERbeta ligands. Part 2: Synthesis and structure-activity relationships of a series of 4-hydroxy-biphenyl-carbaldehyde oxime derivatives", Bioorg. Med. Chem. 12(10), 2553-70.
|
|
Yang, W., et al. (2004b). "Synthesis and structure-activity relationship of 3-arylbenzoxazines as selective estrogen receptor beta agonists", Bioorg. Med. Chem. Lett. 14(9), 2327-30.
|
|
Yepuru et al.; "Estrogen Receptor-β-selective Ligands Alleviate High-fat Diet- and Ovariectomy-induced Obesity in Mice", Journal of Biological Chemistry, vol. 285, No. 41, Jul. 23, 201, pp. 31292-31303.
|
|
Yoo, J. et al. (2005). "Synthesis of an estrogen receptor beta-selective radioligand: 5-[18F]fl-uoro-(2R,3S)-2,3-bis(4-hydroxyphenyl)pentanenitrile and comparison of in vivo distribution with 16alpha-[18F]fluoro-17beta-estradiol". J. Med. Chem. 48(20), 6366-78.
|
|
Yu et al, "Inflamattory components of adipose tissue as target for treatment of metabolic syndrome", 2009 Forum. Nutr. 61:95-103.
|
|
Yu, H. P., et al. (2006). "Salutary effects of estrogen receptor-beta agonist on lung injury after trauma-hemorrhage", Am. J. Physiol. Lung. Cell Mol. Physiol. 290(5), L1004-9.
|
|
Zhou, H. B, et al. (2005). "Synthesis and evaluation of estrogen receptor ligands with bridged oxabicyclic cores containing a diarylethylene motif: estrogen antagonists of unusual structure". J. Med. Chem. 48(23), 7261-74.
|
